results from the Phase III ELEVATE TN trial showed 93% of patients on Calquence combined with obinutuzumab vs. 47% of patients on chlorambucil plus obinutuzumab remained free of disease progression or death at 24 months Trial also showed 87% of patients on Calquence alone
remained free of disease progression or death at 24 months
AstraZeneca today presented results from the interim analysis of the Phase III ELEVATE TN trial, showing that Calquence (acalabrutinib) combined with obinutuzumab or as monotherapy significantly improved progression-free survival (PFS) compared to chlorambucil plus obinutuzumab, a standard chemo-immunotherapy treatment, in patients with previously untreated chronic lymphocytic leukaemia (CLL).1
The Independent Review Committee (IRC)-assessed results were presented at the 2019
In an exploratory analysis, Calquence in combination or alone demonstrated consistent PFS improvements across most pre-specified subgroups of patients with high-risk disease characteristics, including the unmutated immunoglobulin heavy-chain variable gene (IGHV), del(11q) and complex karyotype. Overall, the safety and tolerability profile of Calquence observed in the ELEVATE TN trial was consistent with its known profile.1
Dr.
Summary of key efficacy results as assessed by IRC from the ELEVATE TN trial at a median follow-up of 28.3 months:1
CI, confidence interval; NR, not reached; NE, not estimable; HR, hazard ratio; ORR, overall response rate;
OS, overall survival
Adverse events (AEs) led to treatment discontinuation in 11.2% of patients treated with Calquence in combination with obinutuzumab and 8.9% of patients treated with Calquence monotherapy versus 14.1% of patients treated with chlorambucil plus obinutuzumab.1
With over two years of follow-up, 79% of patients in both the Calquence-containing arms remain on Calquence as a monotherapy. In the Calquence combination arm (n=178), the most common AEs of any grade (>=30%) included headache (39.9%), diarrhoea (38.8%) and neutropenia (31.5%). In the Calquence monotherapy arm (n=179), the most common AEs of any grade (>=30%) included headache (36.9%) and diarrhoea (34.6%). In the chlorambucil plus obinutuzumab arm (n=169), the most common AEs of any grade (>=30%) included neutropenia (45.0%), infusion-related reaction (39.6%) and nausea (31.4%).1
SPM, secondary primary malignancy; NMSC, non-melanoma skin cancer
These findings, along with previously reported data from the Phase III ASCEND trial in relapsed or refractory CLL, support the recent approvals of Calquence by the
About Calquence
In the US and
Calquence is a next-generation selective inhibitor of Bruton's tyrosine kinase (BTK). It binds covalently to BTK, thereby inhibiting its activity.2,3,4,5 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.2
As part of an extensive clinical development programme, AstraZeneca and
About ELEVATE TN
ELEVATE TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of Calquence in combination with obinutuzumab, a CD20 monoclonal antibody, or Calquence alone versus chlorambucil, a chemotherapy, in combination with obinutuzumab in previously untreated patients with CLL. Patients 65 years of age or older, or between 18 and 65 years of age with a total Cumulative Illness Rating Scale (CIRS) >6 or creatinine clearance of 30 to 69 mL/min, were enrolled. In the trial, 535 patients were randomised (1:1:1) into three arms. Patients in the first arm received chlorambucil in combination with obinutuzumab. Patients in the second arm received Calquence (100mg approximately every 12 hours until disease progression or unacceptable toxicity) in combination with obinutuzumab. Patients in the third arm received Calquence monotherapy (100mg approximately every 12 hours until disease progression or unacceptable toxicity).1,6
The primary endpoint is PFS in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee (IRC), and a key secondary endpoint is IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm. Other secondary endpoints include objective response rate, time to next treatment and overall survival.1,6
About CLL
Chronic lymphocytic leukaemia (CLL) is one of the most common types of leukaemia in adults, with an estimated 105,000 new cases globally in 2016 and 20,720 new cases in the US in 2019, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.7,8,9,10 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.7 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.7 This could result in anaemia, infection and bleeding.7 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
About AstraZeneca in haematology
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About AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca's main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in
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1. Sharman JP, et al. ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone vs O Plus Chlorambucil (Clb) in Patients (Pts) With Treatment-Naive Chronic Lymphocytic Leukemia (CLL). Abstract 31 at:
2. CALQUENCE® (acalabrutinib) [prescribing information].
3. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).
4. Khan Y & O'Brien S. Acalabrutinib and its use in treatment of chronic lymphocytic leukemia. Future Oncol. 2018;15(6).
5. Byrd JC, et al. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016; 374:323-332.
6. ClinicalTrials.gov. Elevate CLL TN: Study of Obinutuzumab + Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL. NCT02475681. Available online. Accessed
7.
8. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016. JAMA Oncol. 2018;4(11):1553-1568.
9.
10. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126:871.
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